Neuropsychology, Neuroimage and Neurophysiology in Adults With ADHD

NCT ID: NCT02642068

Last Updated: 2021-09-02

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 300 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-08-01
• Study Completion Date: 2019-07-31

Brief Summary

We anticipate that drug-naïve ADHD probands, particularly those with DAT1 or SLC6A2 gene variants may have higher level of altered microstructural integrity of frontostriatal (FS), frontoparietal (FP), other hypothesized fiber tracts and decreased brain activity of FS, FP, and other circuits, deficits in ERP, and impaired EF, SA, IIA and VM than probands without DAT1 or SLC6A2 gene variants or adult neurotypical. The alterations in the structural and functional connectivity, neurophysiological and neuropsychological functioning would be observed in the unaffected siblings as compared to neurotypical. The unaffected siblings will be in the intermediate position between drug-naïve adult ADHD probands and neurotypical. The genetic dosage is anticipated to pose the strongest effects on the cortical thickness, brain volume, gyrification and microstructural property of white matter, followed by neurophysiology, functional connectivity, and neuropsychological function with the least effect.

In terms of longitudinal follow-up part, we also anticipated despite increasing thinning of cortical thickness, microstructural integrity of several targets fiber tracts, and brain activity of target brain regions and improving performance in EF, SA, IIV, VM from childhood to late adolescence and young adulthood in the neurotypical group, the slopes of developmental trajectories of these neuroimaging and neuropsychological function are lower in the ADHD group.

Detailed Description

Attention deficit/hyperactivity disorder (ADHD) is a common (3-10%), early-onset, clinically and genetically heterogeneous neuropsychiatric disorder with lifelong neuropsychological deficits. Despite extensive research in adult ADHD in western countries, there has been no published data about adult ADHD in Taiwan except the PI's and colleagues' previous works on pharmacotherapy in adults with ADHD and only few endophenotype studies based on adults with ADHD in the world. The ultimate goals of this 5-year project are to identify which neuropsychological, functional and structural connectivity, and neurophysiological variables can be effective endophenotypes (biomarkers) for ADHD based on unaffected sibling (1st-3rd years) and follow-up (4th-5th years) designs. With the accomplishment of the following study goals, this study will be the first study on the topics of neuroimaging and neurophysiological endophenotypes on adult ADHD using advanced imaging techniques (i.e., Tract-based autonomic analysis, TBAA) and comprehensive clinical and neurocognitive data. This proposal has one primary aim and four secondary aims:

Primary Aim:

1. To validate structural (assessed by TBAA using diffusing spectrum imaging, DSI) and functional connectivity (assessed by resting-state fMRI) in frontostriatal, frontoparietal and other circuitries, and neurophysiological functions (assessed by stop-signal event-related potential [ERP]: N2, P3, ERN, Pe) as effective imaging endophenotypes by demonstrating the intermediate position of unaffected siblings between ADHD probands, and age-, sex-, handedness-, and IQ-matched adult neurotypical and association with DAT1 and NET (SLC6A2) variants;

Secondary Aims:

2. To validate the executive functions (EF), sustained attention (SA), intraindividual variability (IIV), visual-spatial memory (VM) as effective neurocognitive endophenotypes by demonstrating the intermediate position of unaffected siblings between ADHD probands, and adult neurotypical;

3. To examine the developmental trajectory and stability of neuropsychological functions and structural and functional connectivity from childhood to adolescence and young adulthood;

4. To correlate the data from structural (morphometric, cortical thickness, gyrification, fiber tract integrity) and functional connectivity (rsfMRI), neuropsychology (Executive function, visual-spatial memory, sustained attention, variability), neurophysiology (Stop-signal ERP) and ADHD core symptoms stratifying by the presence of ADHD, presence of DAT1 and NET (SLC6A2) variants, proband-unaffected sibling dyads, and different developmental stages.

Conditions

Attention Deficit Hyperactivity Disorder

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

ADHD group

Drug-naïve adult ADHD Probands

No interventions assigned to this group

Sibling group

Unaffected Siblings of Drug-naïve Adult ADHD

No interventions assigned to this group

Control group

Age-, sex-, handedness-, and IQ-matched controls without lifetime ADHD or a family history of ADHD

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Subjects aged 16-30, who have clinical diagnosis of a ADHD according to the DSM-IV and DSM-5 diagnostic criteria, and who have never been treated with medication for ADHD treatment. At least 30 out of 60 subjects have same-sex unaffected siblings.

Exclusion Criteria

• The subjects will be excluded from the study if they meet any of the following criteria: (1) Comorbidity with DSM-IV-TR or DSM-5 diagnoses of autism spectrum disorder, schizophrenia, schizoaffective disorder, delusional disorder, other psychotic disorder, organic psychosis, schizotypal personality disorder, bipolar disorder, depression, severe anxiety disorders or substance use; (2) With neurodegenerative disorder, epilepsy, involuntary movement disorder, congenital metabolic disorder, brain tumor, history of severe head trauma, and history of craniotomy; (3)With visual or hearing impairments, or motor disability which may influence the process of MRI assessment; and (4) Full-scale IQ lower than 80.

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Taiwan University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Susan Shur-Fen Gau, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital & College of Medicine

Locations

National Taiwan Univeristy Hospital

Taipei, , Taiwan

Countries

Taiwan

References

Lee CY, Goh JOS, Gau SS. Differential neural processing of value during decision-making in adults with attention-deficit/hyperactivity disorder and healthy controls. J Psychiatry Neurosci. 2023 Mar 29;48(2):E115-E124. doi: 10.1503/jpn.220123. Print 2023 Mar-Apr.

Reference Type: DERIVED

PMID: 36990469 (View on PubMed)

Other Identifiers

201401024RINC

Identifier Type: -

Identifier Source: org_study_id